Xenopus oocytes are an excellent model system for studying Ca signaling. The purpose of this study was to characterize in detail the Ca-activated Cl currents evoked by injection of inositol 1,4,5-trisphosphate (IP3) into Xenopus oocytes voltage-clamped with two microelectrodes. Injection of IP3 into Xenopus oocytes activates two different Ca-activated Cl currents. ICl-1 is stimulated rapidly (within 5 s after IP3 injection), exhibits time-dependent activation upon depolarization, a linear instantaneous IV relationship with a reversal potential near ECl, and a curvilinear activation curve with an approximate half-maximal activation voltage of > 200 mV. ICl-2D is stimulated slowly after IP3 injection (half-maximal stimulation occurs approximately 3 min after injection). ICl-2D has a strongly outwardly rectifying instantaneous IV relationship with a reversal potential near ECl and is activated by hyperpolarization with a half-maximal activation voltage of -105 mV. ICl-2D cannot be activated by Ca released from stores but is activated by Ca influx. In contrast, ICl-1 can be stimulated by Ca released from intracellular Ca stores. It can also be stimulated by Ca influx through store-operated channels if the Ca driving force is increased by a hyperpolarization immediately before the depolarization that gates ICl-1 channels. The description of two currents activated by influx and Ca release from stores provides new insights into and questions about the regulation of Ca in Xenopus oocytes.

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